Establishment of brain metastatic model of NS CLC and investigation for the mechanism of brain metastasis of NS CLC

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671326
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Wakayama Medical University
• Principal Investigator: YOSHIMASU Tatsuya Wakayama Medical University Department of Thoracic and Cardiovascular Surgery Instructor, 医学部, 助手 (60316099)
• Co-Investigator(Kenkyū-buntansha): SAKAGUCHI Kazunari Wakayama Medical University Institute of Advanced Medicine Professor, 付置研究所, 教授 (60178548) ; MATSUURA Nariaki Osaka University School of Allied Health Sciences Professor, 医学部・保健学科, 教授 (70190402)
• Project Period (FY): 2000 – 2002
• Keywords: Lung Cancer / Brain Metastasis / Integrin / Laminin

Research Abstract

The aim of this study was to clarify the roles of integrin and extracellular matrix (ECM) in the process of non-small cell lung cancer (NSCLC) brain metastasis. We established an in vivo model of brain metastasis of human NSCLC cell line EBC-1/original in athymic mice, and established highly brain metastatic subdone EBC-1/brain and highly bone metastatic subdone EBC-1/bone. Integrin expression of these subdones was evaluated by flowcytometry. In vitro cell attachment, migration and proliferation assays with ECMs were performed using these subdones. Expression of integrin alpha 3 subunit was higher in EBC-1/brain than in both EBC-1/original and EBC-1/bone. In vitro cell attachment, migration, and proliferation assays revealed that EBC-1/brain had higher affinity and higher reactivity to laminin than EBC-1/original and EBC-1/bone. Blocking of integrin a3b1 significantly (p<0.05) decreased brain metastasis by EBC-1/brain. Interaction of integrin alpha 3 beta 1 and laminin plays important roles in the process of brain metastasis of non-small cell lung cancer.